This technology introduces a novel nano-formulation of Mithramycin A designed to improve cancer treatment effectiveness while significantly reducing associated liver toxicity.
Mithramycin A (MithA) is a potent inhibitor of RNA synthesis that binds to DNA and has demonstrated effectiveness against a specific oncogene found in Ewing sarcoma, a rare and aggressive cancer. Despite its therapeutic potential, clinical use of MithA was discontinued due to severe liver toxicity and undesirable side effects such as thrombocytopenia. This limitation created a need for a safer delivery system that could preserve the drug's anti-cancer properties without causing harmful systemic effects.
This invention presents a nano-formulation of Mithramycin A, termed MANP, which conjugates MithA to a polyethylene glycol (PEG) polymer through an acid-cleavable boronate linker. This design allows MANP to remain stable in the bloodstream but facilitates controlled release of active MithA in the acidic tumor microenvironment. By targeting drug release specifically to tumor sites, this approach minimizes exposure to healthy liver tissue, thus reducing liver toxicity and thrombocytopenia. Preclinical studies have demonstrated that MANP maintains potent anti-tumor activity against Ewing sarcoma while extending the survival of treated mice without the toxic effects observed with free MithA administration. This formulation enhances therapeutic efficacy and safety by improving drug bioavailability, minimizing off-target toxicity, and leveraging tumor-specific conditions for precise drug activation.
Photo for reference only, not a depiction of the invention.
• Significantly decreases liver toxicity and thrombocytopenia compared to traditional Mithramycin A treatment.
• Maintains strong anti-tumor efficacy against Ewing sarcoma by targeted drug release in the tumor microenvironment.
• Utilizes a PEG polymer conjugation and acid-cleavable linker to allow controlled and tumor-specific drug activation.
• Enhances patient safety and treatment tolerability, potentially enabling higher or more sustained dosing.
• Preclinical evidence supports improved survival outcomes in tumor-bearing models without adverse effects.
• Treatment of Ewing sarcoma and potentially other cancers driven by DNA-binding oncogenes susceptible to Mithramycin A.
• Development of safer chemotherapy options by reducing systemic toxicities associated with powerful anti-cancer drugs.
• Use in targeted nano-drug delivery platforms where controlled release in acidic tumor environments is desired.
• Potential integration into combinational cancer therapies to improve efficacy and reduce side effects.
Patent application filed, 17/890,125
https://patents.google.com/patent/US20230233695A1/en
TRL 3 – Experimental Proof of Concept
This technology is available for licensing.